ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.340+574A>T

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001344145 SCV001538181 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2020-04-27 criteria provided, single submitter clinical testing This sequence change falls in intron 1 of the VHL gene. It is not expected to change the encoded amino acid sequence of the VHL protein. However, this sequence change falls within a cryptic exon in the VHL gene, known as exon E1’, which is naturally expressed at low levels in several human tissues. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has been observed in an individual with erythrocytosis (PMID: 29891534). In this individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. Experimental studies have shown that this variant disrupts the relative levels of naturally occurring VHL mRNA isoforms, increasing expression of exon E1’ containing isoforms and decreasing the expression of the major mRNA isoforms of VHL which do not contain exon E1’ (PMID: 29891534). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.